1. Technical Field
The present invention relates to methods, compositions and devices for intravascular engraftment in heart and other organs.
2. Background Information
Cardiovascular disease includes dysfunctional conditions of the heart, arteries, and veins that supply oxygen to vital life-sustaining areas of the body like the brain, the heart itself, and other vital organs. Lack of oxygen can result in tissue or organ death. Common forms of cardiovascular disease include heart disease and stroke, the first and third leading causes of death for both men and women in the United States, accounting for approximately forty percent of all deaths. About sixty-one million Americans have some form of cardiovascular disease, with about 650,000 Americans dying of cardiovascular disease each year.
Vascular occlusions, such as chronic total occlusions (CTOs), are leading contributors of various vascular diseases, including but not limited to, cardiovascular disease, vascular disease, peripheral artery disease and artherosclerosis.
A CTO in a vasculature of a body and especially peripheral vascular and coronary arteries has life or limb threatening effects for a patient. A CTO is a condition in which the occluding material substantially blocks the cross section of the vasculature over a variable length of the vasculature. The CTO substantially stops blood flow through the vasculature and can result in oxygen deprivation to the tissue near the occlusion. The CTOs can occur throughout the arterial system of the body. Because the coronary arteries, classified as “end circulation,” represent the only source of blood supply to the myocardium, i.e., cardiac muscle cells, the blockage of these vessels can be especially critical.
Although numerous methods and devices, including devices that push through the occlusion to open the vessel (see for example, U.S. Pat. No. 6,579,302) and devices that cross a total occlusion in a blood vessel (see for example, U.S. Pat. No. 6,235,000), have been proposed to treat CTOs, these devices or methods only address the issue of re-establishing oxygenated blood flow to the underperfused viable tissue or non-viable tissue that may have resulted from the limited supply or lack of oxygen due to the CTO.
To date, some methods of treating damaged myocardium have been proposed. For example, one method includes providing pharmaceutical therapies in an effort to restore heart function. However, such therapies may not be particularly effective if the damage to the heart is too severe, and pharmaceutical therapy is not believed to regenerate cardiomyocytes, but instead acts to block or promote certain molecular pathways that are thought to be associated with the progression of heart disease to heart failure.
Another method includes “cell therapy.” Cell therapy involves the administration of endogenous, autologous and/or or nonautologous cells to a patient. For example, myogenic cells can be injected into damaged cardiac tissue with the intent of replacing damaged heart muscle or improving the mechanical properties of the damaged region.
There are several strategies for cell delivery in cardiac cell therapy. The cells can be delivered through coronary arteries or coronary veins. Alternatively, direct intramyocardial injection can be performed, using a surgical, transendocardial, or transvenous approach. See for example, Sherman W., et al., “Catheter-based delivery of cells to the heart,” Nature Clinical Practice Cardiovascular Medicine (2006) 3, S57-S64; Perin E. C. and Lopez J., “Methods of stem cell delivery in cardiac diseases,” Nature Clinical Practice Cardiovascular Medicine (2006) 3, S110-S113; Freyman T., et al., “A Quantitative, Randomized Study Evaluating Three Methods of Mesenchymal Stem Cell Delivery Following Myocardial Infarction,” European Heart Journal Advance Access (2006) 27(9), 1114-1122; and Oron U., et al., “Technical Delivery of Myogenic Cells Through an Endocardial Injection Catheter for Myocardial Cell Implantation,” Int J Cardiovasc Intervent. (2000) 3(4), 227-230.
There are, however, some limitations to such cell therapies. For example, one limitation of seeding the myocardium with intravascular (coronary artery) injection is that the coronary flow though the area seeded with cells; the transplanted cells can be washed downstream before a significant or desired number of cells could establish or engraft themselves in the area of injured myocardium. In addition, the current cell therapies are not localized to the diseased target area and allow for systemic spill over and potential for side effects. Accordingly, there is need in the art for enhanced efficacy of cell therapies and methods and therapies that would allow localized delivery of the cells to the treatment area. This localized delivery will then allow the cells to engraft, divide and establish themselves and function at the site of implantation.